Leakage of mitochondrial and cytosolic GOT in isolated rat hepatocytes exposed to halothane: An immunohistochemical study

The leakage of mitochondrial (m-) and cytosolic (s-) aspartate aminotransferases (glutamic-oxaloacetic transaminase: GOT) from isolated hepatocytes exposed to halothane was investigated immunohistochemically. In control isolated hepatocytes, a large number of cells were immunopositive (m-GOT, 85%; s-GOT, 98.5%) at various intensities. Reaction products of m-GOT-immunohistochemistry (m-GOT-I) were seen exclusively in mitochondria, while those of s-GOT (s-GOT-I) were seen in the cytoplasm. When treated with low concentrations of halothane (up to 0.75%), the number of strongly m-GOT-I-immunopositive cells was reduced to half, while that of s-GOT-I showed no noticeable change. The number of m-GOT-I-immunonegative cells showed a negligible increase, while that of s-GOT-I increased gradually. At higher concentrations of halothane (1% or more), strongly immunopositive cells in both m- and s-GOT-I almost disappeared, while immunonegative cell numbers predominantly increased. This study showed that the isolated hepatocyte system was not homogeneous with regard to the quantity of GOT isozymes, and that halothane could induce the leakage of these isozymes from hepatocytes, along with inducing ultrastructural abnormalities, even at the lowest concentration used (0.5%). Furthermore, the data appear to indicate that the sensitivity of isolated hepatocytes to halothane is dependent on the nature of the hepatocyte itself and on the nature of both types of GOT isozymes.